Hair cells, the receptors of the internal ear, are the mechanical sensors responsible for converting sounds and accelerations into electrical signals that can then be forwarded to the brain for interpretation. Because over 30 million Americans suffer from significant hearing problems, it is important both that we understand how these cells function normally and that we to learn why they are so vulnerable, how they may be protected, and whether they can be repaired or even regenerated after damage. The present studies are meant to explore three important aspects of hair-cell function. The initial set of experiments should provide an understanding of the basis of the cochlear active process that normally sensitizes and tunes our auditory responsiveness, and whose failure leaves us "hard of hearing." Advanced image-processing techniques will be used to determine how mechanical stimuli stemming from sounds make their way through the complex mechanical apparatus of the cochlea and to the hair cells. Interferometric experiments will disclose how these signals propagate through each hair cell's mechanical- receptor organelle, the hair bundle, to initiate an electrical response. A second group of investigations involves the mechanism by which hair cells transmit information to the nerve fibers of the eighth cranial nerve, the conduit from the ear to the brain. Here physiological techniques will provide a means of ascertaining the mechanism of synaptic signaling between hair cells and nerve terminals. In addition, biochemical and molecular-biological approaches will be used to identify novel proteins involved in synaptic signaling by hair cells and to establish their functional roles. The final experiments are intended to demonstrate how the ear becomes organized during development so that the hair cells responsive to each successive frequency, or pure tone, are sequentially arranged along the length of the cochlea. This investigation should provide insight into the biochemical basis for specifying the identity of individual hair cells and may suggest effective techniques for fostering their regeneration. [unreadable] [unreadable] [unreadable]